Використання хмарних технологій в освіті

GCVAR in core, accessory and whole genomes. (PDF 31 kb

Naturally occurring Neisseria gonorrhoeae can have large deletions in housekeeping gene abcZ, making them untypable with multilocus sequence typing

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The effect of recombination on the evolution of a population of Neisseria meningitidis

Neisseria meningitidis (the meningococcus) is a major human pathogen with a history of high invasive disease burden, particularly in sub-Saharan Africa. Our current understanding of the evolution of meningococcal genomes is limited by the rarity of large-scale genomic population studies and lack of in-depth investigation of the genomic events associated with routine pathogen transmission. Here, we fill this knowledge gap by a detailed analysis of 2839 meningococcal genomes obtained through a carriage study of over 50,000 samples collected systematically in Burkina Faso, West Africa, before, during, and after the serogroup A vaccine rollout, 2009-2012. Our findings indicate that the meningococcal genome is highly dynamic, with highly recombinant loci and frequent gene sharing across deeply separated lineages in a structured population. Furthermore, our findings illustrate how population structure can correlate with genome flexibility, as some lineages in Burkina Faso are orders of magnitude more recombinant than others. We also examine the effect of selection on the population, in particular how it is correlated with recombination. We find that recombination principally acts to prevent the accumulation of deleterious mutations, although we do also find an example of recombination acting to speed the adaptation of a gene. In general, we show the importance of recombination in the evolution of a geographically expansive population with deep population structure in a short timescale. This has important consequences for our ability to both foresee the outcomes of vaccination programs and, using surveillance data, predict when lineages of the meningococcus are likely to become a public health concern.Peer reviewe

Evolution of Bordetella pertussis in the acellular vaccine era in Norway, 1996 to 2019

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Percorsi adriatici. Mobilità studentesca e dinamiche sociali tra le universitates della Puglia, Padova e Venezia (XV-XVI secolo)

Questa ricerca si concentra sulla mobilit\ue0 di studenti che, muovendo dai territori della Puglia storica tra il XV e il XVI secolo, scelsero lo Studio di Padova come sede privilegiata per la propria formazione accademica, facendo tappa anche presso quelli di Ferrara e Bologna. Tale fenomeno si inscrive nel quadro di secolari e costanti rapporti politici, commerciali e culturali lungo l\u2019area adriatica. L\u2019incrocio della variegata documentazione rintracciata - documentazione di carattere universitario, registri di notai, raccolte documentarie come i Codici Diplomatici e i Libri Rossi, Cronache locali - unita alla bibliografia sul tema, ha fatto emergere una vasta gamma di notizie, che sono state analizzate e sviluppate nel corso dei capitoli. La prima parte della ricerca costituisce una presentazione del caso di studio, delle questioni storiografiche che sono alla base, delle metodologie adottate. La seconda parte prende in esame i contesti sociali e culturali di provenienza degli studenti, i luoghi e le modalit\ue0 della formazione in patria e quelli della successiva formazione universitaria. La terza parte si concentra esclusivamente sugli attori di questa particolare forma di mobilit\ue0: si ricostruiscono le estrazioni sociali, i casi di tradizioni familiari di studi, le reti di relazioni costruite, le carriere intraprese con il titolo di dottore. La quarta ed ultima parte si concretizza in un catalogo di studenti e dottori pugliesi, dove sono raccolte tutte le notizie di carattere biografico rintracciate. La ricerca si conclude con una appendice documentaria e con l\u2019elenco delle fonti e la bibliografia.This research concentrate on student mobility from Apulian cities during the XV and the XVI century, in particular towards Padua\u2019s Studium, but also towards Ferrara and Bologna. This phenomenon belongs in the secular and political, economic, cultural relationships in the Adriatic area. Sources utilized \u2013 universitary documentation, notarial acts, Codici Diplomatici and Libri Rossi, local chronicles \u2013 and bibliography, are important for informations analised during the research. The first part is a presentation of the case-study, historiographical questions and methodologies. The second part analise social and cultural context of students and their local and universitary studies. The third part is concentrated on students: their social origin, family traditions of studies, social relationships, careers. The fourth part is a catalogue of Apulian students and doctors, with biographical informations. The last part contained documentation and the list of sources and the bibliography

Antibiotic treatment regimes as a driver of the global population dynamics of a major gonorrhea lineage

The Neisseria gonorrhoeae multilocus sequence type (ST) 1901 is among the lineages most commonly associated with treatment failure. Here, we analyze a global collection of ST-1901 genomes to shed light on the emergence and spread of alleles associated with reduced susceptibility to extended-spectrum cephalosporins (ESCs). The genetic diversity of ST-1901 falls into a minor and a major clade, both of which were inferred to have originated in East Asia. The dispersal of the major clade from Asia happened in two separate waves expanding from ∼1987 and 1996, respectively. Both waves first reached North America, and from there spread to Europe and Oceania, with multiple secondary reintroductions to Asia. The ancestor of the second wave acquired the penA 34.001 allele, which significantly reduces susceptibility to ESCs. Our results suggest that the acquisition of this allele granted the second wave a fitness advantage at a time when ESCs became the key drug class used to treat gonorrhea. Following its establishment globally, the lineage has served as a reservoir for the repeated emergence of clones fully resistant to the ESC ceftriaxone, an essential drug for effective treatment of gonorrhea. We infer that the effective population sizes of both clades went into decline as treatment schemes shifted from fluoroquinolones via ESC monotherapy to dual therapy with ceftriaxone and azithromycin in Europe and the United States. Despite the inferred recent population size decline, the short evolutionary path from the penA 34.001 allele to alleles providing full ceftriaxone resistance is a cause of concern

Rapid phenotypic evolution in multidrug-resistant Klebsiella pneumoniae hospital outbreak strains

L. v. D., L. P. S., X. D., H. W. and F. B. acknowledge financial support from the Newton Trust UK–China NSFC initiative (grants MR/P007597/1 and 81661138006). F. B. acknowledges support from the BBSRC GCRF scheme. H. W. additionally acknowledges support from China NSFC grant 81625014. H. C. acknowledges financial support from a 111 Talent Discipline Planning of PKUPH award for a 1-year visit at University College London. Data statement: All supporting data, code and protocols have been provided within the article or through supplementary data files. Nine supplementary tables and fifteen supplementary figures are available with the online version of this article.Peer reviewedPublisher PD

Detection of a reservoir of bedaquiline / clofazimine resistance associated variants in Mycobacterium tuberculosis predating the antibiotic era

Drug resistance in tuberculosis (TB) poses a major ongoing challenge to public health. The recent inclusion of bedaquiline into TB drug regimens has improved treatment outcomes, but this advance is threatened by the emergence of strains of Mycobacterium tuberculosis (Mtb) resistant to bedaquiline. Clinical bedaquiline resistance is most frequently conferred by resistance-associated variants (RAVs) in the Rv0678 gene which can also confer cross-resistance to clofazimine, another TB drug. We compiled a dataset of 3,682 Mtb genomes, including 223 carrying Rv0678 bedaquiline RAVs. We identified at least 15 cases where RAVs were present in the genomes of strains collected prior to the use of bedaquiline in TB treatment regimes. Phylogenetic analyses point to multiple emergence events and circulation of RAVs in Rv0678, often prior to the introduction of bedaquiline or clofazimine. We also identify one case where the RAV Ile67fs is estimated to have emerged prior to the antibiotic era. The presence of a pre-existing reservoir of bedaquiline-resistant Mtb strains augments the need for rapid drug susceptibility testing and individualised regimen selection to safeguard the use of bedaquiline in TB care and control